Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells

Table 1

Examples of HA-decorated lipid-based nanocarriers for targeting of CD44.

Carrier	Drug	HA	Main findings	Reference
Liposomes	DOX	LMW-HA	Avid cell-liposome binding followed by internalization in cells overexpressing CD44.; Higher cytotoxicity compared with free drug on CD44-overexpressing cells.	[12]
Liposomes	MMC; DOX	HMW-HA	Higher affinity of HMW-HA to bind the CD44 receptors, compared to hyaluronan fragments.; Long-term circulation of HMW-HA liposomes.; HMW-HA can act as cryoprotectant, thus allowing liposome lyophilization.; Loading into the HA-modified liposomes generates a 100-fold increase in drug potency in tumor cells overexpressing CD44 receptors.; Higher drug accumulation in tumor, compared to free drug or drug in unmodified liposomes.	[13, 14]
Self-assembled lipid nanoparticles	PTX	HMW-HA	Reduced PTX accumulation in liver and spleen and increased drug accumulation in the tumor, compared to Taxol.; Prolonged PTX half-life.; Reduced PTX toxicity.	[15]
HA-coated nanostructured lipid carriers	PTX	HMW-HA	More effective than Taxol with fewer side effects.; Prolonged PTX half-life.; Increased PTX accumulation in tumors.	[16]
Self-assembled nanoparticles	DCT	LMW-HA	Enhanced intracellular DCT uptake in the CD44-overexpressing cell lines.; MDR-overcoming effects.; In vivo specific CD44-mediated tumor targeting.	[17]
PEGylated self-assembled nanoparticles	DOX		Improved retention time in the bloodstream and nanoparticle accumulation at the tumor site.; PEGylation resulted in prolonged nanoparticle circulation and reduced DOX clearance rate.; Higher in vivo antitumor efficacy in the tumor xenograft mouse model in comparison to non-PEGylated nanoparticles and DOX alone.	[18]
Cationic liposomes	DNA and siRNA	HMW-HA	The presence of HA-DOPE lipid conjugate in the liposome composition did not affect the lipoplex formation.; Increased nucleic acid protection against enzymatic degradation.; Increased the level of transfection on CD44-highly expressing cells.	[19–21]
Nanoparticles	—	Different molecular weights	No induction of complement activation.	[18]